Polydactyly is typically observed as isolated and sporadic occurrences, although familial cases do exist, albeit with lower frequency, manifesting in various inheritance patterns. In around 30% of polydactyly cases, there exists a familial history, suggesting the probable involvement of a single gene. Given its potential for hereditary transmission, thorough investigation of the patients' parents, first-degree relatives, grandparents, and even great-grandparents for similar disorders becomes imperative. In our clinic, we conducted an analysis focusing on patients presenting with foot polydactyly, along with occurrences of polydactyly among their first- and second-degree relatives spanning two to three generations of family history. The study encompassed three patients and their respective families, including a pair of siblings. We speculate that the inheritance type in our cases was autosomal dominant. Among our patients, one presented with central polydactyly, while the remaining patients and all familial cases displayed postaxial polydactyly. In terms of morphologic classification, one patient had a Y-shaped metatarsal, another had a T-shaped metatarsal, and the third patient exhibited a duplicated ray-shaped anomaly. In our review of the literature, we haven't come across a case spanning three generations like the ones we encountered. Additionally, the presence of a transverse accessory extensor tendon between both extensor tendons in cases with T- and Y-shaped metatarsals intrigued us from an anatomical perspective. Our goal is to present these rare cases of congenital familial polydactyly spanning three generations, highlighting the anatomical variations observed and aiming to contribute to the existing body of literature on the subject.

This systematic review and meta-analysis evaluated the safety of montelukast in treating asthma during pregnancy, focusing on maternal and fetal outcomes such as congenital anomalies (CA), preterm delivery, low birthweight, spontaneous abortion, gestational diabetes mellitus, and preeclampsia. A comprehensive literature search was conducted in Google Scholar, PubMed, and the Cochrane Library databases from inception until April 30, 2024. The eligible studies assessed the safety of montelukast for asthma treatment during pregnancy. The review suggests that montelukast use during pregnancy may not significantly increase the risk of major CA. The pooled results yielded risk ratio (RR) for CA was 1.13 [95% CI (0.74, 1.73), p = 0.56, I = 0%]. Montelukast may be associated with preterm delivery and a low birthweight odds ratio (OR) of 1.82 [95% CI (1.35, 2.45), p < 0.001, I = 0%]. No significant risks were found concerning neurodevelopmental outcomes. The associations with spontaneous abortion were inconclusive [OR = 1.03, 95% CI (0.72, 1.5), p = 0.86, I = 73%], highlighting the need for further research. This comprehensive review underscores the importance of further investigating the safety profile of montelukast during pregnancy. While the overall findings indicate a relatively favorable safety profile, especially regarding major CA, careful consideration is needed for the potential risks of preterm delivery and low birthweight.

Lung involvement in children with congenital cytomegalovirus infection has been scarcely described. We describe three new cases of persistent pulmonary hypertension in children with congenital cytomegalovirus and review the other seven cases reported in the literature since 1988. All children had a symptomatic infection, including severe central nervous system or visceral findings. Morbidity and mortality were high. Persistent pulmonary hypertension may be a rare complication in severely symptomatic congenital cytomegalovirus infants. It is important to screen for congenital cytomegalovirus in cases of idiopathic refractory persistent pulmonary hypertension. Intensive treatment should be undertaken to treat this potentially rare lung involvement in combination with antiviral treatment.

The usefulness and effectiveness of telepractice have been reported in recent years. Treatment of cleft palate patients with compensatory articulation is based on perceptual identification. Telepractice using videoconferencing platforms causes voice signal distortion and impacts auditory-perceptual perception. This study aimed acoustically examine voice signal distortion and determine the optimal videoconferencing platforms, in addition to the phonemes that can be discriminated with the same quality as in face-to-face interactions. ATR503 with 50 phoneme-balanced Japanese speech sentences was used as a reference corpus. Four videoconferencing platforms, -Zoom, Cisco Webex, Skype, and Google Meet, -and five devices, -iPhone, Android, iPad Air, Windows, and MacBook Pro were used as transmission conditions to examine voice signal distortions with the objective measure log-spectral distortion (LSD). Tukey's test was conducted to evaluate the degree of consonant distortion related to voicings (voiceless and voiced), places of articulation (bilabial, alveolar, alveolo-palatal, palatal, velar, labial-velar, and glottal), and manners of articulation (plosive, fricative, affricate, tap or flap, nasal, and approximant). With statistically significant differences, voiced, bilabial, labial-velar, nasal, and plosive consonants exhibited smaller distortions. In contrast, voiceless, alveolo-palatal, fricative, and affricate consonants exhibited larger distortions. Google Meet exhibited the lowest distortion among videoconferencing platforms and MacBook exhibited the lowest distortion among devices. This study provides significant insights into the telepractice strategies with the appropriate videoconferencing platform and device, and useful settings for cleft palate patients with compensatory articulations with respect to acoustics.

There is an increase in the worldwide prevalence of congenital abdominal wall defects (CAWD), with gastroschisis (GS) and omphalocele (OC) being the most common. It is widely accepted that folic acid supplementation (FAS) in the maternal diet decreases the incidence of anomalies such as neural tube defects, but there is controversy regarding the possible beneficial role for other congenital malformations. Several epidemiological studies raise controversy regarding a possible relationship between vitamin supplementation with the occurrence of abdominal wall malformations. The aim of the present study is to obtain an updated review of the global frequency of CAWD in neonates and the relationship with FAS in the mothers. For this we have carried out a systematic search of epidemiological studies in different article databases between 2011 and 2022. The analysis of 25 studies conducted in different countries where cases of OC and/or GS are registered directly or together with other congenital defects shows that 60% inquire into the relationship of FAS with the incidence of CAWD. Half of them proposes a beneficial effect of FAS and the other half find no association, concluding that there is no unanimous evidence that FAS in the maternal diet decreases the incidence of CAWD. However, it seems that an influential factor to take into account is the nutritional habits of the mothers.

This pharmacovigilance study investigated the relationship between antiepileptic drugs and congenital strabismus, utilizing the FDA Adverse Event Report System database between 2014 and 2023. Out of 28 347 889 reports of adverse events in 10 937 764 cases, we identified 1104 reports of strabismus and 67 of congenital strabismus. Valproic acid was the most frequently implicated primary suspect drug (95 and 14 cases, respectively). Ninety-five reports involved transplacental valproic acid exposure, yielding an information component (IC) of 7.06 (IC-2 × standard deviation: 5.50). A multivariate analysis showed that transplacental exposure to valproic acid correlated with strabismus (adjusted odds ratio: 8.47, 95% CI: 6.74-10.65). We revealed a robust safety signal linking valproic acid to congenital strabismus.

Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help and advice on drug use at two teratology information institutes in Japan. The primary endpoint of the study was the incidence of major congenital anomalies. The study population included pregnant women exposed to (i) fluoroquinolones (fluoroquinolone group), (ii) β-lactams (infectious control group), or (iii) other agents considered to be nonteratogenic in humans (nonteratogenic control group) during the first trimester. The frequency of major congenital anomalies was compared across groups using a logistic regression model that adjusted for maternal age, smoking status, drinking status, facility consulted, and time of consultation. The fluoroquinolone group consisted of 411 women who had 383 children born alive. The infectious control and nonteratogenic control groups consisted of 1416 and 1482 women who had 1322 and 1401 children born alive, respectively. The incidence of major congenital anomalies was 1.5%, 2.0%, and 1.6% in the fluoroquinolone group, infectious control, and nonteratogenic control groups, respectively. Logistic regression showed that fluoroquinolone exposure is not a significant risk factor for major congenital anomalies. In conclusion, first-trimester exposure to fluoroquinolone antibiotics was not associated with increased maternal or fetal risks.

We experienced an atypical case of radial longitudinal deficiency that did not fit into any classifications, including Blauth. The patient had a bilateral hypoplastic thumb, in which the index and middle fingers were missing in the right hand. We performed surgeries in four stages: centralization of the right hand, opponensplasty of the right thumb, opponensplasty of the left thumb, and distraction lengthening of the right ulnar. Twenty-five years after the initial treatment, the patient was satisfied with the treatment and had no significant difficulty with activities of daily living.

A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole-exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia.

During pregnancy, the maternal environment is critical for normal ontogeny and central nervous system development. Occasionally, prenatal exposure to environmental factors affects tissue architecture and functional development of the brain, which causes developmental disorders, including disorders of the autism spectrum. One of these environmental factors is the exposure to infectious diseases during pregnancy. In this study, we generated mice with infectious disease-induced inflammation by prenatal exposure to 200 μg/kg polyinosinic-polycytidylic acid sodium salt [Poly(I:C)] at embryonic day 12.5 and analyzed their phenotypes on 30-weeks-old. We attempted to detect abnormalities in spontaneous activity and social interaction, which may be indicators of developmental disorder-like behavioral abnormalities, in free-ranging behaviors in multiple rearing environments using multiple animal positioning systems and UMATracker in mice with fetal inflammation. Increased spontaneous activity and abnormal social interactions were observed in mice in the Poly(I:C)-treated group compared with those in the control group. Prenatal exposure to Poly(I:C) increased motor activity and decreased social interaction, and social behavior in prenatally treated mice in a multiple-individual rearing environment. Poly(I:C) exposure during the fetal period resulted in developmental disorder-like behavioral abnormalities, such as increased activity and abnormal social interactions, even after maturation in a multiple-individual rearing environment. This experimental method may provide a new way to analyze the behavior of mouse models of developmental disorders in a multiple-individual rearing environment, in which free-ranging behavior is possible.

Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.

This pictorial essay focuses on ultrasound (US) and magnetic resonance imaging (MRI) features of fetal urogenital anomalies. Fetal urogenital malformations account for 30%-50% of all anomalies discovered during pregnancy or at birth. They are usually detected by fetal ultrasound exams. However, when ultrasound data on their characteristics is insufficient, MRI is the best option for detecting other associated anomalies. The prognosis highly depends on their type and whether they are associated with other fetal abnormalities.

We evaluated the teratogenic risk associated with exposure to cefditoren pivoxil during the first trimester of pregnancy using the integrated databases of the Toranomon Hospital and the National Center for Child Health and Development. Among 13 599 registered individuals, the analysis included 285 subjects who had taken cefditoren pivoxil during the first trimester of pregnancy. The rates of stillbirth, miscarriage, and elective terminations were 0.4%, 5.6%, and 2.1%, respectively. Among 262 live births, the rates of preterm birth, low birth weight, and major congenital malformations were 4.6%, 5.7%, and 1.2%, respectively. Our results suggest that exposure to cefditoren pivoxil during the first trimester of pregnancy does not significantly increase the risk of adverse pregnancy outcomes and infant outcomes.

The objective of this study was to conduct qualitative research by clarifying the thoughts of pregnant women undergoing non-invasive prenatal testing (NIPT) in Japan, to collect evidence to provide information and psychosocial support in genetic counseling (GC). We attempted to conduct qualitative research to provide support for GC and the society in relation to children with special needs, by clarifying the thoughts of pregnant women undergoing NIPT. Between January 2016 and December 2017, we administered an open-ended questionnaire to pregnant Japanese women undergoing NIPT to clarify their ethical views in relation to children with special needs. The target population included 754 pregnant women who described their feelings and thoughts about undergoing NIPT and about children with special needs. Pregnant women undergoing NIPT have a variety of various mixed feelings and concerns. We classified the feelings and thoughts of pregnant women who underwent NIPT into the following four primary categories (multiple classifications): (1) perception about people with special needs (18.0%); (2) relation between NIPT and life selection (22.3%); (3) attitudes towards undergoing NIPT (47.5%); and (4) negative feelings and thoughts about raising children with special needs (48.1%). Most pregnant women undergoing NIPT expressed negative feelings and raising children with special needs. These feelings and thoughts may be one of the reasons why pregnant women undergo NIPT. In GC, it is important to also provide wide information on the social support and the current situation in the actual life of children with special needs.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive leukodystrophy characterized by ichthyosis, intellectual disability, and progressive spastic paralysis caused by biallelic pathogenic variants in the ALDH3A2 gene that encodes the fatty aldehyde dehydrogenase, fatty aldehyde dehydrogenase (FALDH); FALDH catalyzes several metabolic reactions involved in fatty aldehyde oxidation. Only a few studies have been performed to determine the lipid profile of patients with SLS. In a previous postmortem study of the brain of a 65-year-old patient with SLS, lipidomic analysis revealed an accumulation of long-chain unsaturated ether lipid species in the white matter and gray matter. In the present study, we established a disease model using patient-derived neuronal and oligodendrocyte lineage cells to analyze the lipid metabolism and gene expression profiles in SLS. To achieve this, we generated induced pluripotent stem cells (iPSCs) from two patients with the SLS phenotype carrying previously known ALDH3A2 pathogenic variants: One was a compound heterozygote (c.1339A>G:p.(Lys447Glu) and c.57_132dup:p.(Ile45Serfs*34)) and the other was a homozygote (c.1339A>G: p.(Lys447Glu)). The FALDH activity was almost zero in the SLS-iPSC lines established from both patients. Phospholipid analysis of neurospheres, and oligospheres (spheres enriched with oligodendrocyte-lineage cells) derived from the iPSCs by liquid chromatography-mass spectrometry showed accumulation of ether phospholipids in the Sjögren-Larsson patient-derived neurospheres and oligospheres. The results are consistent with the previously reported accumulation of ether lipids in the postmortem brain tissue of an SLS patient. Therefore, iPSCs and iPSC-derived neurospheres and oligospheres established from SLS patients can be useful tools for future pathological analysis of the central nervous system pathophysiology in SLS.